Post-traumatic hyperthermia is commonly seen in head-injured patients and may represent an important secondary injury mechanism. This project employs an extensively characterized fluid-percussion model of brain injury to evaluate the neurobehavioral, histopathological and molecular biological consequences of delay post-traumatic hyperthermia. Our first aim is to determine the temporal pattern of naturally occuring brain and core temperature alterations after traumatic injury using continuous telemetric monitoring procedures. Mechanisms underlying abnormal elevations in post- traumatic brain temperatures including the role of the cytokine interleukin-1 will then be investigated. In the second aim the effects of post-trauma temperature alterations on regional patterns of diffuse axonal damage will be examined. We will determine whether a period of delayed hyperthermia or immediate post-traumatic hypothermia affects the severity of diffuse axonal injury and whether this pathology correlates with neurobehavioral deficits. The effect of post-traumatic hyperthermia on alterations in blood-brain barrier permeability and subsequent edema formation will also be assessed quantitatively. Because temperature- sensitive inflammatory processes may significantly contribute to traumatic outcome the effects of brain injury on the induction of endothelial adhesion molecules and the regional accumulation of polymorphonuclear leukocytes will be examined. Finally to determine whether a secondary hyperthermic period aggravates outcome by free radical-mediated processes, the effects of post-traumatic hyperthermia on the generation of hydroxyl radicals will be assess by the salicylate trapping method in conjunction with microdialysis and HPLC to detect hydroxyl radicals by measurement of the stable adducts 2.3 and 2.5-dihydroxybenzoic acid (DHBA). Thus, thi project makes extensive use of post-traumatic temperature manipulations to investigate the pathology of traumatic brain injury. In addition, new information regarding the importance of secondary temperature elevations on traumatic outcome will be generated that could have profound implications on the clinical management of head-injured patients.